Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

A Tropospheric Assessment of the ERA-40, NCEP, and JRA-25 Global Reanalyses in the Polar Regions

The reliability of the global reanalyses in the polar regions is investigated. The overview stems from an April 2006 Scientific Committee on Antarctic Research (SCAR) workshop on the performance of global reanalyses in high latitudes held at the British Antarctic Survey. Overall, the skill is much higher in the Arctic than the Antarctic, where the reanalyses are only reliable in the summer months prior to the modern satellite era. In the Antarctic, large circulation differences between the reanalyses are found primarily before 1979, when vast quantities of satellite sounding data started to be assimilated. Specifically for ERA-40, this data discontinuity creates a marked jump in Antarctic snow accumulation, especially at high elevations. In the Arctic, the largest differences are related to the reanalyses depiction of clouds and their associated radiation impacts; ERA-40 captures the cloud variability much better than NCEP1 and JRA-25, but the ERA-40 and JRA-25 clouds are too optically thin for shortwave radiation. To further contrast the reanalyses skill, cyclone tracking results are presented. In the Southern Hemisphere, cyclonic activity is markedly different between the reanalyses, where there are few matched cyclones prior to 1979. In comparison, only some of the weaker cyclones are not matched in the Northern Hemisphere from 1958-2001, again indicating the superior skill in this hemisphere. Although this manuscript focuses on deficiencies in the reanalyses, it is important to note that they are a powerful tool for climate studies in both polar regions when used with a recognition of their limitations

Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports

BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26–34 years old; mean BMI was 30.4 kg/m(2). 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women

An assessment of the Jenkinson and Collison synoptic classification to a continental mid-latitude location

A weather-type catalogue based on the Jenkinson and Collison method was developed for an area in south-west Russia for the period 1961--2010. Gridded sea level pressure data was obtained from the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis. The resulting catalogue was analysed for frequency of individual types and groups of weather types to characterise long-term atmospheric circulation in this region. Overall, the most frequent type is anticyclonic (A) (23.3 {%}) followed by cyclonic (C) (11.9 {%}); however, there are some key seasonal patterns with westerly circulation being significantly more common in winter than summer. The utility of this synoptic classification is evaluated by modelling daily rainfall amounts. A low level of error is found using a simple model based on the prevailing weather type. Finally, characteristics of the circulation classification are compared to those for the original JC British Isles catalogue and a much more equal distribution of flow types is seen in the former classification

Towards a fair comparison of statistical and dynamical downscaling in the framework of the EURO-CORDEX initiative

Both statistical and dynamical downscaling methods are well established techniques to bridge the gap between the coarse information produced by global circulation models and the regional-to-local scales required by the climate change Impacts, Adaptation, and Vulnerability (IAV) communities. A number of studies have analyzed the relative merits of each technique by inter-comparing their performance in reproducing the observed climate, as given by a number of climatic indices (e.g. mean values, percentiles, spells). However, in this paper we stress that fair comparisons should be based on indices that are not affected by the calibration towards the observed climate used for some of the methods. We focus on precipitation (over continental Spain) and consider the output of eight Regional Climate Models (RCMs) from the EURO-CORDEX initiative at 0.44? resolution and five Statistical Downscaling Methods (SDMs) ?analog resampling, weather typing and generalized linear models? trained using the Spain044 observational gridded dataset on exactly the same RCM grid. The performance of these models is inter-compared in terms of several standard indices ?mean precipitation, 90th percentile on wet days, maximum precipitation amount and maximum number of consecutive dry days? taking into account the parameters involved in the SDM training phase. It is shown, that not only the directly affected indices should be carefully analyzed, but also those indirectly influenced (e.g. percentile-based indices for precipitation) which are more difficult to identify. We also analyze how simple transformations (e.g. linear scaling) could be applied to the outputs of the uncalibrated methods in order to put SDMs and RCMs on equal footing, and thus perform a fairer comparison.We acknowledge the World Climate Research Programme’s Working Group on Regional Climate, and theWorking Group on CoupledModelling, former coordinating body of CORDEX and responsible panel for CMIP5. We also thank the climate modeling groups (listed in Table 1 of this paper) for producing and making available their model output. We also acknowledge the Earth System Grid Federation infrastructure and AEMET and University of Cantabria for the Spain02 dataset (available at http: //www.meteo.unican.es/en/datasets/spain02). All the statistical downscaling experiments have been computed using theMeteoLab software (http://www.meteo.unican.es/software/meteolab), which is an open-source Matlab toolbox for statistical downscaling. This work has been partially supported by CORWES (CGL2010-22158-C02) and EXTREMBLES (CGL2010-21869) projects funded by the Spanish R&D programme. AC thanks the Spanish Ministry of Economy and Competitiveness for the funding provided within the FPI programme (BES-2011-047612 and EEBB-I-13-06354), JMG acknowledges the support from the SPECS project (FP7-ENV-2012-308378) and JF is grateful to the EUPORIAS project (FP7-ENV-2012-308291). We also thank three anonymous referees for their useful comments that helped to improve the original manuscript

Foxf2: A Novel Locus for Anterior Segment Dysgenesis Adjacent to the Foxc1 Gene

Anterior segment dysgenesis (ASD) is characterised by an abnormal migration of neural crest cells or an aberrant differentiation of the mesenchymal cells during the formation of the eye's anterior segment. These abnormalities result in multiple tissue defects affecting the iris, cornea and drainage structures of the iridocorneal angle including the ciliary body, trabecular meshwork and Schlemm's canal. In some cases, abnormal ASD development leads to glaucoma, which is usually associated with increased intraocular pressure. Haploinsufficiency through mutation or chromosomal deletion of the human FOXC1 transcription factor gene or duplications of the 6p25 region is associated with a spectrum of ocular abnormalities including ASD. However, mapping data and phenotype analysis of human deletions suggests that an additional locus for this condition may be present in the same chromosomal region as FOXC1. DHPLC screening of ENU mutagenised mouse archival tissue revealed five novel mouse Foxf2 mutations. Re-derivation of one of these (the Foxf2W174R mouse lineage) resulted in heterozygote mice that exhibited thinning of the iris stroma, hyperplasia of the trabecular meshwork, small or absent Schlemm's canal and a reduction in the iridocorneal angle. Homozygous E18.5 mice showed absence of ciliary body projections, demonstrating a critical role for Foxf2 in the developing eye. These data provide evidence that the Foxf2 gene, separated from Foxc1 by less than 70 kb of genomic sequence (250 kb in human DNA), may explain human abnormalities in some cases of ASD where FOXC1 has been excluded genetically

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007

Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques

A Systematic Review of the Prevalence of Schizophrenia

BACKGROUND: Understanding the prevalence of schizophrenia has important implications for both health service planning and risk factor epidemiology. The aims of this review are to systematically identify and collate studies describing the prevalence of schizophrenia, to summarize the findings of these studies, and to explore selected factors that may influence prevalence estimates. METHODS AND FINDINGS: Studies with original data related to the prevalence of schizophrenia (published 1965–2002) were identified via searching electronic databases, reviewing citations, and writing to authors. These studies were divided into “core” studies, “migrant” studies, and studies based on “other special groups.” Between- and within-study filters were applied in order to identify discrete prevalence estimates. Cumulative plots of prevalence estimates were made and the distributions described when the underlying estimates were sorted according to prevalence type (point, period, lifetime, and lifetime morbid risk). Based on combined prevalence estimates, the influence of selected key variables was examined (sex, urbanicity, migrant status, country economic index, and study quality). A total of 1,721 prevalence estimates from 188 studies were identified. These estimates were drawn from 46 countries, and were based on an estimated 154,140 potentially overlapping prevalent cases. We identified 132 core studies, 15 migrant studies, and 41 studies based on other special groups. The median values per 1,000 persons (10%–90% quantiles) for the distributions for point, period, lifetime, and lifetime morbid risk were 4.6 (1.9–10.0), 3.3 (1.3–8.2), 4.0 (1.6–12.1), and 7.2 (3.1–27.1), respectively. Based on combined prevalence estimates, we found no significant difference (a) between males and females, or (b) between urban, rural, and mixed sites. The prevalence of schizophrenia in migrants was higher compared to native-born individuals: the migrant-to-native-born ratio median (10%–90% quantile) was 1.8 (0.9–6.4). When sites were grouped by economic status, prevalence estimates from “least developed” countries were significantly lower than those from both “emerging” and “developed” sites (p = 0.04). Studies that scored higher on a quality score had significantly higher prevalence estimates (p = 0.02). CONCLUSIONS: There is a wealth of data about the prevalence of schizophrenia. These gradients, and the variability found in prevalence estimate distributions, can provide direction for future hypothesis-driven research

Measurement of electrons from beauty-hadron decays in pp and Pb-Pb collisions at sNN=5.02 TeV

The production of electrons from beauty-hadron decays was measured at midrapidity in proton-proton (pp) and central Pb-Pb collisions at center-of-mass energy per nucleon-nucleon pair √s NN = 5.02 TeV, using the ALICE detector at the LHC. The cross section measured in pp collisions in the transverse momentum interval 2 < pT < 8 GeV/c was compared with models based on perturbative quantum chromodynamics calculations. The yield in the 10% most central Pb-Pb collisions, measured in the interval 2 < pT < 26 GeV/c, was used to compute the nuclear modification factor RAA, extrapolating the pp reference cross section to pT larger than 8 GeV/c. The measured R AA shows significant suppression of the yield of electrons from beauty-hadron decays at high pT and does not show a significant dependence above 8 GeV/c within uncertainties. The results are de- scribed by several theoretical models based on different implementations of the interaction of heavy quarks with a quark-gluon plasma, which predict a smaller energy loss for beauty quarks compared to light and charm quark

Investigation of K+K- interactions via femtoscopy in Pb-Pb collisions at sNN =2.76 TeV at the CERN Large Hadron Collider

Femtoscopic correlations of nonidentical charged kaons (K+K-) are studied in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=2.76 TeV by ALICE at the CERN Large Hadron Collider. One-dimensional K+K- correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K- analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K- correlation functions using the femtoscopic technique. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the φ(1020) meson peak present in the K+K- correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the φ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by final-state interactions could not be precisely quantified with data presented in this paper and will be assessed in future work